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simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
Hepatitis Virus C (HVC) protease inhibitors	4812	923604-59-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: olysio TMC-435 TMC435350 simeprevir simeprevir sodium	Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS. Molecular weight: 749.94 Formula: C38H47N5O7S2 CLOGP: 5.45 LIPINSKI: 3 HAC: 12 HDO: 2 TPSA: 156.89 ALOGS: -5.39 ROTB: 7 Status: OFM Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

olysio
TMC-435
TMC435350
simeprevir
simeprevir sodium

Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.

Molecular weight: 749.94
Formula: C38H47N5O7S2
CLOGP: 5.45
LIPINSKI: 3
HAC: 12
HDO: 2
TPSA: 156.89
ALOGS: -5.39
ROTB: 7

Status: OFM

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.15	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Hosey CM, Chan R, Benet LZ

Approvals:

Date	Agency	Company	Orphan
May 14, 2014	EMA
Nov. 22, 2013	FDA	JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	761.49	35.46	301	4414	100425	50499984
Anaemia	561.84	35.46	325	4390	252131	50348278
White blood cell count decreased	460.22	35.46	221	4494	116501	50483908
Blood bilirubin increased	380.59	35.46	134	4581	31904	50568505
Neutrophil count decreased	275.48	35.46	117	4598	45909	50554500
Haemoglobin decreased	211.83	35.46	137	4578	127079	50473330
Hyperbilirubinaemia	164.68	35.46	53	4662	9517	50590892
Haemolytic anaemia	145.84	35.46	48	4667	9244	50591165
Hepatitis C	108.72	35.46	33	4682	4884	50595525
Hepatocellular carcinoma	107.63	35.46	27	4688	1972	50598437
Pruritus	103.10	35.46	129	4586	283439	50316970
Off label use	102.17	35.46	168	4547	474258	50126151
Pyrexia	91.80	35.46	142	4573	380061	50220348
Photosensitivity reaction	84.29	35.46	35	4680	12876	50587533
Remission not achieved	52.61	35.46	9	4706	94	50600315
Decreased appetite	45.38	35.46	73	4642	200850	50399559
Hepatic failure	42.08	35.46	30	4685	32253	50568156
Hepatic function abnormal	41.75	35.46	30	4685	32651	50567758
Jaundice	40.18	35.46	27	4688	26402	50574007
Sunburn	40.04	35.46	13	4702	2390	50598019
Hepatic encephalopathy	39.93	35.46	19	4696	9617	50590792
Hepatitis C RNA increased	37.37	35.46	7	4708	126	50600283
Depressive symptom	36.39	35.46	13	4702	3187	50597222

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	543.91	28.88	300	5265	104372	29464590
White blood cell count decreased	391.23	28.88	224	5341	83138	29485824
Blood bilirubin increased	351.15	28.88	156	5409	33737	29535225
Anaemia	309.56	28.88	273	5292	200678	29368284
Hepatitis C	286.94	28.88	94	5471	8816	29560146
Hepatocellular carcinoma	254.09	28.88	81	5484	6957	29562005
Off label use	214.24	28.88	271	5294	300529	29268433
Hyperbilirubinaemia	171.31	28.88	74	5491	14860	29554102
Neutrophil count decreased	144.17	28.88	94	5471	43473	29525489
Haemoglobin decreased	143.66	28.88	136	5429	108239	29460723
Photosensitivity reaction	140.34	28.88	56	5509	9202	29559760
Drug ineffective	95.94	28.88	210	5355	362960	29206002
Jaundice	72.67	28.88	53	5512	29243	29539719
Remission not achieved	71.77	28.88	13	5552	89	29568873
Pruritus	69.47	28.88	97	5468	116752	29452210
Haemolytic anaemia	59.56	28.88	31	5534	9388	29559574
Sunburn	51.69	28.88	17	5548	1603	29567359
Treatment failure	49.93	28.88	47	5518	36892	29532070
Hepatic failure	46.27	28.88	42	5523	31470	29537492
Genotype drug resistance test positive	46.22	28.88	14	5551	1009	29567953
Pyrexia	44.99	28.88	137	5428	287485	29281477
Ascites	44.59	28.88	44	5521	36575	29532387
Viral load increased	44.02	28.88	16	5549	2033	29566929
Hepatitis C RNA increased	42.38	28.88	10	5555	274	29568688
Hepatic encephalopathy	40.27	28.88	27	5538	13008	29555954
Thought blocking	38.29	28.88	8	5557	123	29568839
Bilirubin conjugated increased	38.01	28.88	16	5549	3001	29565961
Rash	34.96	28.88	96	5469	189723	29379239
Choroiditis	34.08	28.88	11	5554	977	29567985
Hyperuricaemia	33.34	28.88	19	5546	6870	29562092

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Platelet count decreased	1351.13	29.50	600	8987	167111	64322034
White blood cell count decreased	894.43	29.50	444	9143	157393	64331752
Anaemia	846.23	29.50	581	9006	378099	64111046
Blood bilirubin increased	681.15	29.50	272	9315	57281	64431864
Neutrophil count decreased	414.02	29.50	210	9377	76986	64412159
Hepatitis C	384.83	29.50	117	9470	10898	64478247
Haemoglobin decreased	357.77	29.50	267	9320	194796	64294349
Hepatocellular carcinoma	357.69	29.50	104	9483	8299	64480846
Hyperbilirubinaemia	313.32	29.50	118	9469	21087	64468058
Haemolytic anaemia	200.18	29.50	79	9508	15974	64473171
Pruritus	156.28	29.50	211	9376	312189	64176956
Photosensitivity reaction	138.31	29.50	63	9524	18110	64471035
Pyrexia	136.87	29.50	273	9314	558371	63930774
Jaundice	105.75	29.50	74	9513	48438	64440707
Remission not achieved	104.73	29.50	21	9566	335	64488810
Off label use	103.00	29.50	263	9324	632543	63856602
Hepatic failure	81.88	29.50	67	9520	55327	64433818
Hepatic encephalopathy	65.10	29.50	40	9547	21026	64468119
Rash	62.64	29.50	179	9408	458370	64030775
Hepatitis C RNA increased	62.53	29.50	14	9573	386	64488759
Bilirubin conjugated increased	60.32	29.50	24	9563	4944	64484201
Ascites	56.20	29.50	57	9530	61944	64427201
Pain	55.92	29.50	8	9579	553503	63935642
Hyperuricaemia	55.23	29.50	28	9559	10163	64478982
Sunburn	54.48	29.50	20	9567	3312	64485833
Decreased appetite	52.97	29.50	124	9463	281165	64207980
Insomnia	48.42	29.50	97	9490	197739	64291406
Malaise	47.69	29.50	148	9439	396099	64093046
Hepatorenal syndrome	45.14	29.50	18	9569	3728	64485417
Aspartate aminotransferase increased	43.78	29.50	70	9517	119718	64369427
Red blood cell count decreased	41.15	29.50	43	9544	48343	64440802
Hepatic function abnormal	40.72	29.50	49	9538	64264	64424881
Hepatic cirrhosis	39.23	29.50	32	9555	26266	64462879
Viral load increased	37.26	29.50	14	9573	2473	64486672
Thought blocking	36.87	29.50	8	9579	190	64488955
Liver disorder	36.01	29.50	42	9545	53309	64435836
Choroiditis	35.60	29.50	11	9576	1076	64488069
Alanine aminotransferase increased	31.41	29.50	66	9521	138965	64350180
Incorrect product administration duration	31.35	29.50	19	9568	9739	64479406
Injection site dermatitis	31.23	29.50	5	9582	19	64489126

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	J05AP05	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D011480	Protease Inhibitors
FDA MoA	N0000182138	Cytochrome P450 1A2 Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000182638	HCV NS3/4A Protease Inhibitors
FDA EPC	N0000182639	Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA	N0000190108	Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA	N0000190113	Breast Cancer Resistance Protein Inhibitors
FDA MoA	N0000193845	Bile Salt Export Pump Inhibitors
FDA MoA	N0000193960	Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA	N0000193965	Sodium Taurocholate Co-transporting Polypeptide Inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	4.35	acidic
pKa2	6.66	Basic
pKa3	3.5	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8349869	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8741926	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8754106	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9040562	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9353103	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9623022	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	9856265	July 28, 2026	METHOD OF TREATING HEPATITIS C
EQ 150MG BASE	OLYSIO	JANSSEN PRODS	N205123	Nov. 22, 2013	DISCN	CAPSULE	ORAL	8148399	Sept. 5, 2029	METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cathepsin S	Enzyme	P25774	CATS_HUMAN		IC50	6.10	CHEMBL
Hepatitis C virus serine protease, NS3/NS4A	Enzyme		A3EZI9_9HEPC D2K2A8_9HEPC	INHIBITOR	Ki	9.30	CHEMBL	CHEMBL
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	Ki	9.44	SCIENTIFIC LITERATURE	DRUG LABEL
Nonstructural protein NS3-4A	Unclassified		A0A0K1CY61_9HEPC		Ki	9.44	CHEMBL
Polyprotein	Polyprotein		Q6GYR8_9HEPC	INHIBITOR	Ki	9.44	IUPHAR
Genome polyprotein	Unclassified		A3EZJ3_9HEPC		Ki	9.30	CHEMBL

External reference:

ID	Source
D10081	KEGG_DRUG
1241946-89-3	SECONDARY_CAS_RN
4032900	VANDF
CHEBI:134743	CHEBI
30B	PDB_CHEM_ID
CHEMBL501849	ChEMBL_ID
7367	IUPHAR_LIGAND_ID
9432	INN_ID
DB06290	DRUGBANK_ID
9WS5RD66HZ	UNII
24873435	PUBCHEM_CID
1482790	RXNORM
207569	MMSL
29896	MMSL
d08182	MMSL
015309	NDDF
015310	NDDF
708823009	SNOMEDCT_US
714167009	SNOMEDCT_US
D000069616	MESH_DESCRIPTOR_UI
C2605855	UMLSCUI
CHEMBL3137358	ChEMBL_ID

Pharmaceutical products:

None